The detection of antibodies, such as neutralizing antibodies (NAbs), is part of the immunogenicity assessment that this performed for patients treated with a biotherapeutic agent. Neutralizing antibodies neutralize the function of the drug thereby negatively impacting the efficacy of the drug. The presence of NAbs in patients treated with a specific biotherapeutic agent may be detected using several immunoassay methods, including, for example, colorimetric enzyme-linked immunosorbent assay (ELISA), immunofluorescence based receptor binding assays, soluble and solid phase radioimmunoassays, and sensor-based assay.
NAbs can also be detected using cell-based assays. In these cell-based assays, the presence of NAbs can be detected by their ability to inhibit the biological action of the biotherapeutic agent, for example, modulation of a biological process in the target cell. These assays may involve, for example, the activation of a reporter gene, such as luciferase or beta-galactosidase. However, these current detection methods suffer from a number of drawbacks including the level of sensitivity, the level of specificity, matrix interference issues, assay variability, limited dynamic range and the lengthy duration of the assays.
Sarilumab is the first fully human monoclonal antibody targeting the interleukin-6 (IL6) receptor in clinical development. IL-6 is a pleiotropic cytokine produced by immune and non-immune cells that plays a crucial role in regulation of immune response, acute-phase reactions, and hematopoiesis. It binds to soluble and cell membrane bound IL-6R (α chain) forming a binary complex and this complex is able to interact with cell membrane bound gp130 (β chain), induces formation of signaling complex comprising two each of IL-6, IL-6R, and gp130.